Ripoli 2009 J Virol: Difference between revisions
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|title=Ripoli M, D'Aprile A, Quarato G, Sarasin-Filipowicz M, Gouttenoire J, Scrima R, Cela O, Boffoli D, Heim MH, Moradpour D, Capitanio N, Piccoli C (2009) Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible factor 1{alpha}-mediated glycolytic adaptation. J Virol 84: 647- | |title=Ripoli M, D'Aprile A, Quarato G, Sarasin-Filipowicz M, Gouttenoire J, Scrima R, Cela O, Boffoli D, Heim MH, Moradpour D, Capitanio N, Piccoli C (2009) Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible factor 1{alpha}-mediated glycolytic adaptation. J Virol 84:647-60. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/19846525 PMID: 19846525] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/19846525 PMID: 19846525 Open Access] | ||
|authors=Ripoli M, D'Aprile A, Quarato G, Sarasin-Filipowicz M, Gouttenoire J, Scrima R, Cela O, Boffoli D, Heim MH, Moradpour D, Capitanio N, Piccoli C | |authors=Ripoli M, D'Aprile A, Quarato G, Sarasin-Filipowicz M, Gouttenoire J, Scrima R, Cela O, Boffoli D, Heim MH, Moradpour D, Capitanio N, Piccoli C | ||
|year=2009 | |year=2009 |
Revision as of 15:34, 20 March 2015
Ripoli M, D'Aprile A, Quarato G, Sarasin-Filipowicz M, Gouttenoire J, Scrima R, Cela O, Boffoli D, Heim MH, Moradpour D, Capitanio N, Piccoli C (2009) Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible factor 1{alpha}-mediated glycolytic adaptation. J Virol 84:647-60. |
Ripoli M, D'Aprile A, Quarato G, Sarasin-Filipowicz M, Gouttenoire J, Scrima R, Cela O, Boffoli D, Heim MH, Moradpour D, Capitanio N, Piccoli C (2009) J Virol
Abstract: Hepatitis C virus (HCV) infection induces a state of oxidative stress by affecting mitochondrial-respiratory-chain activity. By using cell lines inducibly expressing different HCV constructs, we showed previously that viral-protein expression leads to severe impairment of mitochondrial oxidative phosphorylation and to major reliance on nonoxidative glucose metabolism. However, the bioenergetic competence of the induced cells was not compromised, indicating an efficient prosurvival adaptive response. Here, we show that HCV protein expression activates hypoxia-inducible factor 1 (HIF-1) by normoxic stabilization of its ฮฑ subunit. In consequence, expression of HIF-controlled genes, including those coding for glycolytic enzymes, was significantly upregulated. Similar expression of HIF-controlled genes was observed in cell lines inducibly expressing subgenomic HCV constructs encoding either structural or nonstructural viral proteins. Stabilization and transcriptional activation of HIF-1ฮฑ was confirmed in Huh-7.5 cells harboring cell culture-derived infectious HCV and in liver biopsy specimens from patients with chronic hepatitis C. The HCV-related HIF-1ฮฑ stabilization was insensitive to antioxidant treatment. Mimicking an impairment of mitochondrial oxidative phosphorylation by treatment of inducible cell lines with oligomycin resulted in stabilization of HIF-1ฮฑ. Similar results were obtained by treatment with pyruvate, indicating that accumulation of intermediate metabolites is sufficient to stabilize HIF-1ฮฑ. These observations provide new insights into the pathogenesis of chronic hepatitis C and, possibly, the HCV-related development of hepatocellular carcinoma. โข Keywords: Hepatitis C virus (HCV)
โข O2k-Network Lab: IT Foggia Capitanio N
Labels: MiParea: Respiration
Stress:Hypoxia Organism: Human Tissue;cell: Liver
Enzyme: Uncoupling protein Regulation: Aerobic glycolysis, Inhibitor
HRR: Oxygraph-2k